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Intracellular ATP directly blocks K+ channels in pancreatic B-cells
Abstract
It is known that glucose-induced depolarization of pancreatic B-cells is due to reduced membrane K+-permeability and is coupled to an increase in the rate of glycolysis, but there has been no direct evidence linking specific metabolic processes or products to the closing of membrane K+ channels. During patch-clamp studies of proton inhibition of Ca2+-activated K+ channels [GK(Ca)] in B-cells, we identified a second K+-selective channel which is rapidly and reversibly inhibited by ATP applied to the cytoplasmic surface of the membrane. This channel is spontaneously active in excised patches and frequently coexists with GK(Ca) channels yet is insensitive to membrane potential and to intracellular free Ca2+ and pH. Blocking of the channel is ATP-specific and appears not to require metabolism of the ATP. This ATP-sensitive K+ channel [GK(ATP)] may be a link between metabolism and membrane K+-permeability in pancreatic B-cells.
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“Metabolic regulation of the channel is mediated by changes in the intracellular concentrations of ATP and MgADP, which inhibit and stimulate the channel, respectively (127, 163, 328).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [127]
In the citing paper
“In excised inside-out patches, ATP inhibition is half-maximal at ≈10 μM in the absence of Mg2+ (127), but this increases to 20-30 µM in the presence of Mg2+ due to the simultaneous presence of Mg-nucleotide stimulation via SUR1 (234).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [127]
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Neuronal metabolism governs cortical network response state
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“This ATP alters the basal ATP/ADP ratio, causing the ATP-sensitive K (KATP) channels to close, depolarizing the cell and leading to the opening of Ca2 channels, overall increasing cytoplasmic Ca2 concentration ([Ca2 ]i) (1, 13, 51, 57).”
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“In contrast, in NRAs, ADP and AMP were completely without effect, and half-maximum block was observed with [ATP]i of 0.8 M.”
BackgroundInfluentialMolecular aspects of ATP-sensitive K+ channels in the cardiovascular system and K+ channel openers.
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Potassium channel openers and vascular smooth muscle relaxation.
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“The sensitivity of KATP chan- 1989; Cook and Hales 1984; Kakei et al. 1985; Spruce et al. 1987; Trube and Hescheler 1984).”
Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide.
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Sequence Variants in the Sulfonylurea Receptor (SUR) Gene Are Associated With NIDDM in Caucasians
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“It is now known that signals derived from the metabolism of glucose in pancreatic p-cells lead to a sequence of events that includes closure of ATP-sensitive potassium channels (IKATP); membrane depolarization; activation of voltagegated Ca channels, which results in increased intracellular Ca; and insulin exocytosis…”
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“ATP‐sensitive potassium (KATP) channels were found to couple glucose metabolism to membrane electrical activity and insulin release over 30 years ago (Ashcroft, Harrison, & Ashcroft, 1984; Cook & Hales, 1984; Rorsman & Trube, 1985).”
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Metadata
- Authors
- Cook, D. L., & Hales, N.
- Affiliations
- United States Department of Veterans Affairs (US)
- Venue
- Nature
- Published
- 1984-09
- Volume
- 311
- Issue
- 5983
- Pages
- 271-273
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1985770721
- Cited by
- 1,208
- References
- 24
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 12 · 2023: 22 · 2022: 14 · 2021: 21 · 2020: 12 · 2019: 19 · 2018: 13 · 2017: 9 · 2016: 15 · 2015: 21 · 2014: 34 · 2013: 14 · 2012: 29
- FWCI
- 13.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- ATP-sensitive potassium channels, pancreatic beta cells, intracellular ATP, potassium channel inhibition, glycolysis, proton inhibition, calcium-activated potassium channels
- MeSH terms
- Adenosine Triphosphate, Animals, Cell Membrane Permeability, Cells, Cultured, Cytoplasm, Electric Conductivity, Ion Channels, Islets of Langerhans, Potassium, Rats
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